中国药事
中國藥事
중국약사
Chinese Pharmaceutical Affairs
2015年
10期
1055-1061
,共7页
阿魏酸%高效液相色谱%药代动力学%比格犬血浆
阿魏痠%高效液相色譜%藥代動力學%比格犬血漿
아위산%고효액상색보%약대동역학%비격견혈장
ferulic acid%HPLC%pharmacokinetics%beagle dog plasma
目的：建立高效液相色谱法测定比格犬血浆中阿魏酸的含量，并用于药代动力学研究。方法：血浆样品采用乙酸乙酯处理，以替硝唑作为内标，色谱柱为Phenomenex Luna C18色谱柱，流动相为水（含5 mmol·L-1醋酸铵和0.05%H3PO4）-乙腈（60︰40），等度洗脱，流速为1.0 mL·min-1，紫外检测波长为320 nm。采用比格犬单剂量静注3、6、12 mg·kg-1的阿魏酸， HPLC-UV法测定阿魏酸的血药浓度，并采用DAS 2.0软件计算药代动力学参数。结果：方法学实验结果表明内源性杂质不干扰阿魏酸和内标的测定，线性范围0.0975~12.5μg·mL-1，定量限为0.0975μg·mL-1。方法精密度、准确度、稳定性和回收率均符合生物样品测定的要求，适合比格犬血浆中阿魏酸浓度的测定，可以应用该方法进行阿魏酸的药代动力学研究。比格犬单剂量静注3、6、12 mg·kg-1的阿魏酸后，血药浓度-时间曲线下面积（AUC0-τ）分别为244.81±57.34、508.40±118.82、988.87±172.29 min·μg·mL-1，不同剂量下AUC0-τ比为1︰2.1︰4.0，与剂量比1︰2︰4近似成比例，说明在研究的剂量范围内，阿魏酸在Beagle犬体内的消除过程是线性的。结论：本方法操作简便、灵敏、专属性强，方法学考证符合生物样品测定的要求并成功用于阿魏酸在比格犬体内的药代动力学研究。
目的：建立高效液相色譜法測定比格犬血漿中阿魏痠的含量，併用于藥代動力學研究。方法：血漿樣品採用乙痠乙酯處理，以替硝唑作為內標，色譜柱為Phenomenex Luna C18色譜柱，流動相為水（含5 mmol·L-1醋痠銨和0.05%H3PO4）-乙腈（60︰40），等度洗脫，流速為1.0 mL·min-1，紫外檢測波長為320 nm。採用比格犬單劑量靜註3、6、12 mg·kg-1的阿魏痠， HPLC-UV法測定阿魏痠的血藥濃度，併採用DAS 2.0軟件計算藥代動力學參數。結果：方法學實驗結果錶明內源性雜質不榦擾阿魏痠和內標的測定，線性範圍0.0975~12.5μg·mL-1，定量限為0.0975μg·mL-1。方法精密度、準確度、穩定性和迴收率均符閤生物樣品測定的要求，適閤比格犬血漿中阿魏痠濃度的測定，可以應用該方法進行阿魏痠的藥代動力學研究。比格犬單劑量靜註3、6、12 mg·kg-1的阿魏痠後，血藥濃度-時間麯線下麵積（AUC0-τ）分彆為244.81±57.34、508.40±118.82、988.87±172.29 min·μg·mL-1，不同劑量下AUC0-τ比為1︰2.1︰4.0，與劑量比1︰2︰4近似成比例，說明在研究的劑量範圍內，阿魏痠在Beagle犬體內的消除過程是線性的。結論：本方法操作簡便、靈敏、專屬性彊，方法學攷證符閤生物樣品測定的要求併成功用于阿魏痠在比格犬體內的藥代動力學研究。
목적：건립고효액상색보법측정비격견혈장중아위산적함량，병용우약대동역학연구。방법：혈장양품채용을산을지처리，이체초서작위내표，색보주위Phenomenex Luna C18색보주，류동상위수（함5 mmol·L-1작산안화0.05%H3PO4）-을정（60︰40），등도세탈，류속위1.0 mL·min-1，자외검측파장위320 nm。채용비격견단제량정주3、6、12 mg·kg-1적아위산， HPLC-UV법측정아위산적혈약농도，병채용DAS 2.0연건계산약대동역학삼수。결과：방법학실험결과표명내원성잡질불간우아위산화내표적측정，선성범위0.0975~12.5μg·mL-1，정량한위0.0975μg·mL-1。방법정밀도、준학도、은정성화회수솔균부합생물양품측정적요구，괄합비격견혈장중아위산농도적측정，가이응용해방법진행아위산적약대동역학연구。비격견단제량정주3、6、12 mg·kg-1적아위산후，혈약농도-시간곡선하면적（AUC0-τ）분별위244.81±57.34、508.40±118.82、988.87±172.29 min·μg·mL-1，불동제량하AUC0-τ비위1︰2.1︰4.0，여제량비1︰2︰4근사성비례，설명재연구적제량범위내，아위산재Beagle견체내적소제과정시선성적。결론：본방법조작간편、령민、전속성강，방법학고증부합생물양품측정적요구병성공용우아위산재비격견체내적약대동역학연구。
Objective:To establish a sensitive, simple and specific high-performance liquid chromatography method for determination of ferulic acid in order to study the pharmacokinetics of ferulic acid in beagle dogs. Methods:Ferulic acid and tinidazole (internal standard, IS) were extracted by liquid-liquid extraction and separated on a Phenomenex Luna C18 column, with acetonitrile and water (containing 5 mmol·L-1 ammonium acetate and 0.05% phosphoric acid) (40︰60) as the mobile phase. The lfow rate was set to be 1.0 mL·min-1 and the analytical wavelength was 320 nm. After validating, the developed method was used for evaluating pharmacokinetics of ferulic acid in beagle dogs following intravenous administration of three doses (3, 6,12 mg·kg-1) of ferulic acid. The pharmacokinetic parameters were calculated by the software DAS 2.0.Results: The methodological study showed endogenous impurities did not interfere the determination of ferulic acid, and the internal standard and a good linear relationship were found within 0.0975-12.5 μg·mL-1 with a sensitivity of 0.0975 μg·mL-1 as the limit of quantiifcation. The precision, accuracy, stability and mean recoveries met the requirements of biological sample measurement. The method described above was successfully applied to the pharmacokinetic study of ferulic acid in the samples of beagle dog plasma. The area under the plasma concentration-time curves (AUC0-τ) of ferulic acid after single intravenous doses of 3, 6 and 12 mg·kg-1 was 244.81±57.34, 508.40±118.82, 988.87±172.29 min·μg·mL-1, respectively. The relationship between dose and AUC0-τ showed a good linearity as the AUC0-τ ratio was 1︰2.1︰4.0 under different doses which was proportional to the dose ratio of 1︰2︰4, indicating that the elimination process of ferulic acid in beagle dogs was linear.Conclusion:This HPLC-UV method for determination of ferulic acid was proved to have sufficient selectivity, sensitivity and reproducibility and was successfully applied to the pharmacokinetic study of ferulic acid in beagle dogs.
